Myostatin Mutation Promotes Glycolysis by Increasing Phosphorylation of Phosphofructokinase Activation of PDE5A-cGMP-PKG in Cattle Heart

Overview

Journal Front Cell Dev Biol

Specialty Cell Biology

Date 2022 Feb 14

PMID 35155444

Authors

Mingjuan Gu

Xinyu Zhou

Lin Zhu

Yajie Gao

Li Gao

Chunling Bai

Lei Yang

Guangpeng Li

Affiliations

Soon will be listed here.

Abstract

Myostatin (MSTN) is a primary negative regulator of skeletal muscle mass and causes multiple metabolic changes. However, whether MSTN mutation affects heart morphology and physiology remains unclear. Myostatin mutation (MT) had no effect on cattle cardiac muscle in histological examination, but in biochemical assays, glycolysis increased in cattle hearts with MT. Compared with wild-type cattle, there were no differences in mRNA and protein levels of rate-limiting enzymes, but phosphofructokinase (PFK) phosphorylation increased in cattle hearts with MT. Transcriptome analysis showed that phosphodiesterase-5A (PDE5A), a target for inhibiting cGMP-PKG signaling, was downregulated. For the mechanism, chromatin immunoprecipitation qPCR showed that the SMAD2/SMAD3 complex in the canonical downstream pathway for MSTN combined with the promoter of PDE5A. The cGMP-PKG pathway was activated, and PKG increased phosphorylation of PFK in cattle hearts with MT. In addition, activation of PKG and the increase in PFK phosphorylation promoted glycolysis. Knockdown of PKG resulted in the opposite phenomena. The results indicated that MT potentiated PFK phosphorylation the PDE5A-cGMP-PKG pathway and thereby promoted glycolysis in the heart.

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